2-methyl-3-hydroxy-4-hydroxymethyl pyridine and its acid salts



Patented Nov. 30, 1948 p UNITED STATES PATENT OFFICE Z-METHYL -3- HYDROXY -4- HYDROXY- PYRIDINE AND ITS ACID Gustav J. Martin, Philadelphia, and Souren Avakian, Oreland, Pa., assignors to The National Drug Company, Philadelphia, Pa., a corpora.- tion of Pennsylvania No Drawing. Application April 28, 1947, Serial No. 744,520

3 Claims. (01. 260-297) i 2 Our invention relates to new chemotherapeutic heated at 90-95 C. for three hours and then reagents. More particularly, it concerns the novel fluxed for one hour. The resulting reaction mixcompound, 2-methyl 3 hydi-oxy 4 hydroxyture was dissolved in water, neutralized and exmethyl pyridine, and its salts. tracted with ether. Distillation of the ether ex- We have found that said compounds are high- 5 tract yielded 23 grams of 2-methyl-3-acetoxy-4- ly efiective displacing agents for Vitamin B6 acetoxymethyl pyridine boiling at 135-136" C. un- (pyridoxine). Their ability to displace this vitader a partial vacuum of 0.3 mm. mercury column. min makes them highly useful therapeutically, The hydrochloride of this intermediate melts at whenever it is desired to reduce the absorption of 161-162 C. Vitamin B6 by the body and its effect upon the 10 In the final step 5 grams of the 2-methyl-3- system. The new agents may be administered acetoxy-i-acetoxymethyl pyridine was dissolved in various ways, such as orally and by intramusin 200 cc. of 2 N. hydrochloric acid, and the solucular and intravenous injection. They also aption was refluxed for 12 hours. The solvent was pear to possess certain pharmacological charevaporated under reduced pressure, and the resiacteristics that should make them valuable in 15 due recrystallized from ethyl alcohol. The 2- this department of medicine as well. methyl-3-hydroxy-4-hydroxymethyl pyridine hy- The 2 methyl 3 hydroxyi-hydroxymethyl drochloride so obtained possesses a melting point pyridine may be employed in its free form or in of 165-166 C. The hydrochloride may be conthe form of its salts, particularly the hydrochloverted to the free amine, if desired, by treatment ride. The salts may be prepared in the usual with a dilute, aqueous solution of sodium hymanner, by treating the free amine with various droxide. acids, such as sulfuric acid, acetic acid, etc. The It is apparent that our novel displacing agents free amine may in turn be formed from its salts may be prepared by methods other than the one by treatment in the regular way, with dilute, just disclosed. Our invention is not limited to aqueous alkaline solutions. the foregoing details. It includes the Z-methyl- We have succeeded in preparing the hydro- 3-hydroxy-4-hydroxymethyl pyridine and its chloride of 2-methyl-3-hydroxy-4-hydroxymethyl salts, as well as all obvious equivalents thereof, pyridine from z-picoline (2-methy1 pyridine) by no matter how they may have been prepared. the following series of steps: We claim:

The 2-picoline was first sulfonated and then 1. A compound of the group consisting of 2- fused with caustic alkali according to the methmethyl-3-hydroxy-4-hydroxymethyl pyridine and ods described in the U. S. Patents Nos. 1,880,645 t i n and 1,880,646, in order to produce the 2-methyl 2. 2-methyl-3-hydroxy-4=-hydroxymethyl pyri- 3-hydroxy pyridine. This product was then condine verted to t Y 3 3. The hydrochloride of the compound claimed aminomethyl pyridine according to the method in claim 2 disclosed by Brown and Miller in Journal of Or- GUSTAV JULIUS MARTIN, ganic Chemistry, vol. 11, Part 4, page 388 (1946). SOUREN AVAKIAN,

A solution of 23 grams of the foregoing intermediate in 31 grams of acetic anhydride was No references cited. 

